Abstract
BackgroundThe aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer.MethodsWe enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA.ResultsLevels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor >1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses.ConclusionsOvarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-696) contains supplementary material, which is available to authorized users.
Highlights
The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls
Comparison of serum levels of measured biomarkers between normal controls and ovarian tumor patients Ang-1 levels were 26% and Ang-2 levels were 44% higher in serum samples of ovarian carcinoma patients compared to normal controls (P < 0.05 and P < 0.01, respectively) (Table 1, Figure 1A)
VEGF levels were 44% higher in serum samples of ovarian carcinoma patients compared to patients with benign ovarian tumors (P = 0.054) (Table 1, Figure 1B)
Summary
The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. VEGFs (vascular endothelial growth factors) and their receptors play significant roles in tumor angiogenesis and lymphangiogenesis and are mostly specific to vascular endothelial cells [7,8]. VEGF-A, −B, −C, −D and PLGF signal through three tyrosine kinase receptors VEGFR-1, −2 and −3, known as Flt-1, KDR/Flk-1 and Flt-4 [7]. Both VEGFR-1 and −2 bind VEGF-A, which is the main regulator of blood vessel growth. VEGF-C and-D stimulate lymphangiogenesis through VEGFR-3 which is predominantly expressed in lymphatic endothelium [10,11] and exists in angiogenic sprouts [12]
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